Kamppiper2237

I follow-up of astrocytoma patients, allowing for a significantly higher diagnostic accuracy, particularly for subtle disease progression at a comparable reading time. EVIDENCE LEVEL 3 TECHNICAL EFFICACY STAGE 6. © 2020 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.The unexpected appearance of T1 hyperintensities, mostly in the dentate nucleus and the globus pallidus, during nonenhanced MRI was reported in 2014. This effect is associated with prior repeated administrations of gadolinium (Gd)-based contrast agents (GBCAs) in patients with a functional blood-brain barrier (BBB). It is widely assumed that GBCAs do not cross the intact BBB, but the observation of these hypersignals raises questions regarding this assumption. This review critically discusses the mechanisms of Gd accumulation in the brain with regard to access pathways, Gd species, tissue distribution, and subcellular location. We propose the hypothesis that there is early access of Gd species to cerebrospinal fluid, followed by passive diffusion into the brain parenchyma close to the cerebral ventricles. When accessing areas rich in endogenous metals or phosphorus, the less kinetically stable GBCAs would dissociate, and Gd would bind to endogenous macromolecules, and/or precipitate within the brain tissue. It is also proposed that Gd species enter the brain parenchyma along penetrating cortical arteries in periarterial pial-glial basement membranes and leave the brain along intramural peri-arterial drainage (IPAD) pathways. Lastly, Gd/GBCAs may access the brain parenchyma directly from the blood through the BBB in the walls of capillaries. It is crucial to distinguish between the physiological distribution and drainage pathways for GBCAs and the possible dissociation of less thermodynamically/kinetically stable GBCAs that lead to long-term Gd deposition in the brain. LEVEL OF EVIDENCE 5. TECHNICAL EFFICACY STAGE 3. © 2020 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.Dysfunction of the circadian rhythm is one of most common nonmotor symptoms in Parkinson's disease (PD), but the molecular role of the circadian rhythm in PD is unclear. We here showed that inactivation of brain and muscle ARNT-like 1 (BMAL1) in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-treated mice resulted in obvious motor functional deficit, loss of dopaminergic neurons (DANs) in the substantia nigra pars compacta (SNpc), decrease of dopamine (DA) transmitter, and increased activation of microglia and astrocytes in the striatum. Time on the rotarod or calorie consumption, and food and water intake were reduced in the Bmal1-/- mice after MPTP treatment, suggesting that absence of Bmal1 may exacerbate circadian and PD motor function. We observed a significant reduction of DANs (~35%) in the SNpc, the tyrosine hydroxylase protein level in the striatum (~60%), the DA (~22%), and 3,4-dihydroxyphenylacetic acid content (~29%), respectively, in MPTP-treated Bmal1-/- mice. Loss of Bmal1 aggravated the inflammatory reaction both in vivo and in vitro. These findings suggest that BMAL1 may play an essential role in the survival of DANs and maintain normal function of the DA signaling pathway via regulating microglia-mediated neuroinflammation in the brain. © 2020 Federation of American Societies for Experimental Biology.Bile acids (BAs) have been implicated in regulation of intestinal epithelial signaling and function. This study aimed to investigate the effects of hyodeoxycholic acid (HDCA) on intestinal epithelial cell proliferation and explore the underlying mechanisms. IPEC-J2 cells and weaned piglets were treated with HDCA and the contributions of cellular signaling pathways, BAs metabolism profiles and gut bacteria were assessed. In vitro, HDCA suppressed IPEC-J2 proliferation via the BAs receptor FXR but not TGR5. In addition, HDCA inhibited the PI3K/AKT pathway, while knockdown of FXR or constitutive activation of AKT eliminated the inhibitory effects of HDCA, suggesting that FXR-dependent inhibition of PI3K/AKT pathway was involved in HDCA-suppressed IPEC-J2 proliferation. In vivo, dietary HDCA inhibited intestinal expression of proliferative markers and PI3K/AKT pathway in weaned piglets. Meanwhile, HDCA altered the BAs metabolism profiles, with decrease in primary BA and increase in total and secondary BAs in feces, and reduction of conjugated BAs in serum. Furthermore, HDCA increased abundance of the gut bacteria associated with BAs metabolism, and thereby induced BAs profiles alternation, which might indirectly contribute to HDCA-suppressed cell proliferation. Together, HDCA suppressed intestinal epithelial cell proliferation through FXR-PI3K/AKT signaling pathway, accompanied by alteration of BAs metabolism profiles induced by gut bacteria. © 2020 Federation of American Societies for Experimental Biology.People with intellectual disability (PWID) consistently identify the importance of health service information that is accessible and relevant. Resources tailored to the information and support needs of PWID can facilitate inclusivity in their health care (including access to genomic medicine) and improve healthcare outcomes. Despite the fact that PWID are commonly referred to genetics services, there is a lack of appropriate resources to help them prepare for their appointments. We therefore aimed to evaluate the feasibility and acceptability of a booklet for PWID to read with their carers prior to their genetics appointment, to help them prepare for what they may experience. With input from Easy to Read experts and PWID who were members of the New South Wales (NSW) Council for Intellectual Disability, the information booklet 'Getting ready for your visit to the genetics clinic' was produced. Australian healthcare professionals (HCP) familiar with clinical genetics services were invited to complete an anonymo of Genetic Counselors.BACKGROUND High-frequency (130-185 Hz) deep brain stimulation (DBS) of the subthalamic nucleus is more effective for appendicular than axial symptoms in Parkinson's disease (PD). Low-frequency (60-80 Hz) stimulation (LFS) may reduce gait/balance impairment but typically results in worsening appendicular symptoms. We created a "dual-frequency" programming paradigm (interleave-interlink, IL-IL) to address both axial and appendicular symptoms. In IL-IL, 2 overlapping LFS programs are applied to the DBS lead, with the overlapping area focused on the optimal cathode. The nonoverlapping area (LFS) is thought to reduce gait/balance impairment, whereas the overlapping area (high-frequency stimulation, HFS) aims to control appendicular symptoms. METHODS We performed a randomized, double-blind crossover trial comparing patients' previously optimized IL-IL and conventional HFS paradigms. Each arm was 2 weeks in duration. The primary outcome measure was the patient/caregiver Modified Clinical Global Impression Severity ( Disorder Society. © 2020 International Parkinson and Movement Disorder Society.Investigations of the role of religious philosophy in reproductive decision-making has exclusively focused on Abrahamic traditions. However, those who practice Eastern religions, such as Hinduism, represent an increasing proportion of the population in the United States and may present for prenatal care. Here, we consider tenets of Hindu philosophy as they may pertain to decision-making surrounding women's pregnancy termination. Such tenets include the cycle of rebirth (samsara), karma, dharma, Hindu writing, and the multivalent nature of Hindu philosophy. Through this brief communication we hope to present a starting point for further exploration which will increase cultural competency of genetic counselors while enhancing awareness of variations of religious beliefs patients may hold. © 2020 National Society of Genetic Counselors.BACKGROUND Non-Gaussian diffusion models and T1 rho quantification may reflect the changes in tissue heterogeneity in hepatic sinusoidal obstruction syndrome (SOS). PURPOSE To investigate the feasibility of diffusion kurtosis imaging (DKI), stretched exponential model (SEM), and T1 rho quantification in detecting and staging SOS in a monocrotaline (MCT)-induced rat model. STUDY TYPE Animal study. POPULATION Thirty male Sprague-Dawley rats gavaged with MCT to induce hepatic SOS and six male rats without any intervention. FIELD STRENGTH/SEQUENCE 3.0T, DWI with five b-values (0-2000 s/mm2 ) and T1 rho with five spin lock times (1-60 msec). ASSESSMENT MRI was performed 1 day before and 1, 3, 5, 7, and 10 days after MCT administration. The corrected apparent diffusion coefficient (Dapp ), kurtosis coefficient (Kapp ), distributed diffusion coefficient (DDC), and intravoxel water molecular diffusion heterogeneity (α) were calculated from the corresponding non-Gaussian diffusion model. The T1 rho value was calculateTAGE 2. © 2020 International Society for Magnetic Resonance in Medicine.Over the past 20 years, various identifiers of cellular senescence have been used to quantify the abundance of these cells in different tissues. These include classic markers such as p16, senescence-associated β-gal, and γH2AX, in addition to more recent markers (Sudan Black B and HMGB1). In vivo data on the usefulness of these markers in skeletal muscle are very limited and inconsistent. In the present study, we attempted to identify senescent cells in frozen human skeletal muscle biopsies using these markers to determine the effects of age and obesity on senescent cell burden; however, we were only able to assess the abundance of DNA-damaged nuclei using γH2AX immunohistochemistry. The abundance of γH2AX+ cells, including satellite cells, was not higher in muscle from old compared to young individuals; however, γH2AX+ cells were higher with obesity. Additionally, terminally differentiated, postmitotic myofiber nuclei from obese individuals had elevated γH2AX abundance compared to muscle from lean individuals. Analyses of gene expression support the conclusion that the elevated DNA damage and the senescence-associated secretory phenotype are preferentially associated with obesity in skeletal muscle. These data implicate obesity as a larger contributor to DNA damage in skeletal muscle than aging; however, more sensitive senescence markers for human skeletal muscle are needed to determine if these cells are in fact senescent. © 2020 Federation of American Societies for Experimental Biology.Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified previously in the pathogenesis of hypertension and some gestational diseases. However, the biological functions of MALAT1 in pregnancy-induced hypertension (PIH) are still poorly understood. Herein, we aim to explore the functional relevance of MALAT1 in PIH and to explain the potential underlying mechanisms. We found that the levels of ET-1 and MALAT1 were upregulated and that of miR-150-5p were downregulated in the serum of pregnant women with PIH and the aortic endothelial cells (ECs) of reduced uterine perfusion pressure (RUPP)-induced rat models. In aortic ECs, MALAT1 could competitively bind to miR-150-5p to upregulate the expression of ET-1. The MALAT1/miR-150-5p/ET-1 axis regulated the expression of endothelin B receptor (ETBR) in aortic ECs leading to oxidative stress imbalance and increased the release of proinflammatory cytokines (IL-18 and IL-1β), which concurrently activated the NF-κB pathway to regulate the ETBR expression and to stimulate smooth muscle cell (SMC) contraction.